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Microfluidics for sperm analysis and selection

Reza Nosrati is an NSERC postdoctoral fellow in the Department of Chemical Engineering at Queen's University, Canada. He received his PhD in 2016 from the University of Toronto, Canada, where he discovered the 2D slither swimming mode for sperm near surfaces. His research interests focus on the development and application of microfluidic technologies for male infertility diagnosis, assisted reproduction, cell biology, and biosensing.

Percival J. Graham is a PhD candidate in the Department of Mechanical and Industrial Engineering at the University of Toronto, Canada. His graduate research encompasses microfluidics, male infertility, multiphase flow, high-throughput screening, and photosynthesis.

Biao Zhang is a postdoctoral fellow at the Department of Mechanical and Industrial Engineering at the University of Toronto, Canada. His research interests include the application of biomicrofluidics for assisted reproductive technologies, ranging from point-of-care male fertility potential testing to sperm selection.

Jason Riordon is a research associate at the Department of Mechanical and Industrial Engineering at the University of Toronto, Canada. His research interests include the design and development of microfluidic and nanofluidic lab-on-chip technologies that address challenges in health and energy.

Alexander Lagunov is a hands-on laboratory director at CCRM Toronto/Hannam Fertility Centre located in Toronto, Canada. His research interests include the optimization of sperm selection techniques in assisted reproductive technologies as well as embryo genetics and the search for precise, noninvasive methods of embryo quality assessment.

Tom Hannam is the director and founder of the Hannam Fertility Centre in Toronto, Canada. Dr Hannam obtained his MD from the University of British Columbia and completed his training (FRCSC) in obstetrics and gynaecology at McMaster University, followed by a two-year fellowship in reproductive endocrinology and infertility at the University of Toronto, Canada. He is a renowned expert in fertility treatment and assisted reproductive technology.

Carlos Escobedo is an assistant professor at the Department of Chemical Engineering at Queen's University and Chair of Nanotechnology, MEMS and Microfluidics in the Canadian Society for Mechanical Engineering (CSME). His research programme is dedicated to develop nanofluidic, microfluidic, and optofluidic technologies that enable advances in biology and medicine.

Keith Jarvi is the director of the Murray Koffler Urologic Wellness Centre and Head of Urology at Mount Sinai Hospital, Toronto, Canada. He is professor of surgery and directs the Male Infertility Program at the University of Toronto. Dr Jarvi's research interests include the development of biomarkers to diagnose male reproductive system disorders including male infertility, prostatitis and prostate cancer.

David Sinton is a professor, tier 1 Canada research chair, and NSERC E.W.R. Steacie Memorial fellow in the Department of Mechanical and Industrial Engineering at the University of Toronto, Canada. Dr Sinton's research involves the study and application of small-scale fluid mechanics (microfluidics, nanofluidics, and optofluidics) for use in energy and health applications.

Subjects

Abstract

Infertility is a growing global health issue with far-reaching socioeconomic implications. A downward trend in male fertility highlights the acute need for affordable and accessible diagnosis and treatment. Assisted reproductive technologies are effective in treating male infertility, but their success rate has plateaued at ∼33% per cycle. Many emerging opportunities exist for microfluidics — a mature technology in other biomedical areas — in male infertility diagnosis and treatment, and promising microfluidic approaches are under investigation for addressing male infertility. Microfluidic approaches can improve our fundamental understanding of sperm motion, and developments in microfluidic devices that use microfabrication and sperm behaviour can aid semen analysis and sperm selection. Many burgeoning possibilities exist for engineers, biologists, and clinicians to improve current practices for infertility diagnosis and treatment. The most promising avenues have the potential to improve medical practice, moving innovations from research laboratories to clinics and patients in the near future.

Key points

Sperm swim using periodic but time-irreversible and unidirectional flagellar motion. When sperm swim near a boundary, hydrodynamic sperm–wall interactions result in surface accumulation and boundary-following behaviour

Microfluidic techniques paired with high-speed imaging have resolved the full 3D swimming patterns of sperm in bulk fluid and revealed a 2D slither swimming mode for sperm near surfaces

Microfluidics show promise in studying sperm rheotaxis and chemotaxis. Future research needs to focus on developing high-throughput platforms with single-cell-analysis capabilities to study human sperm chemotaxis

Microfluidic technologies are emerging as rapid and low-cost diagnostic alternatives for at-home and clinical male fertility testing, and technologies for additional, automated morphological analysis of sperm are needed

Microfluidic platforms enable selection of high-quality sperm by mimicking the in vivo process. These technologies show promise for near-term advances in both understanding male infertility and clinical implementation

Translation of microfluidic technologies for male infertility into the consumer market and clinical practices has been slow. A combination of multidisciplinary collaborations and market opportunity will speed up this process

Ishijima, S., Sekiguchi, K. & Hiramoto, Y.Comparative study of the beat patterns of American and Asian horseshoe crab sperm: evidence for a role of the central pair complex in forming planar waveforms in flagella. Cytoskeleton9, 264–270 (1988).

Acknowledgements

This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC I2IPJ469164-14, NSERC RGPIN-2015-06701), Canadian Institutes of Health Research (CIHR 139088), the Ontario Centres of Excellence (169411), and MaRS Innovation. The authors also gratefully acknowledge an NSERC E.W.R. Steacie Memorial Fellowship (DS), the Canada Research Chairs Program (DS), an NSERC postdoctoral fellowship (RN), and a Queen's University postdoctoral fund (RN).